1. Field of the Invention
The present invention relates to pharmaceutical preparations for treating psoriasis comprising a combination of substances based on 1,8,9-anthracenetriol and urea. The preparations are particularly useful for treating psoriasis on the head and other hairy body parts, by the method of short-time therapy.
2. Description of the Related Art
Psoriasis is among the dermatoses having a poorly understood etiology. The therapies of choice are thus topical agents such as salicyclic acid, tars (pices var.), vitamin A acid, corticosteroids, etc. Sometimes, coal tar is used.
Among the agents long used for treating psoriasis is 1,8,9-anthracenetriol (also called dithranol or Anthralin), and certain of its acyl derivatives, usually in preparations containing 0.1-5% by weight of this agent.
The only pharmaceutical forms in which the therapeutic agents are available are lipophilic preparations for local therapy, due to the high instability of the active ingredients against air, oxygen, water, and alkalies. These strongly fattening preparations have relatively low storage stability. They are necessarily inconvenient to use because clothing as well as washrags are strongly dyed by the active ingredient, dithranol. Further, the hydrophobic preparations are difficult to wash off of the skin, particularly in hairy areas.
A psoriasis patient's use of the customary preparations (which were intended for treating non-hairy parts of the skin) in hairy parts leads to a number of problems. If an ointment comprising Vaseline, salicylic acid (2-3%), and dithranol (0.5-3%) is used on, e.g. skin in the hairy area of the head, vigorous rubbing is needed to provide proper contact. This rubbing causes appreciable pain to the affected skin, which already has lesions. Further, due to complications, the treatment must often be performed by hospital personnel.
An optimal therapeutic preparation for treating psoriasis should enab-e concurrent action of urea and dithranol (Eur. A No. 6,724). It is probable that the antipsoriatic action is not solely due to dithranol. Clinical research indicates that the urea, via its multiple effects such as keratolysis and horny layer (stratum corneum) hydration, which effects are known, acts on the epidermis to ameliorate the interference with proper epithelial formation caused by psoriasis.
Another important consideration in treating psoriasis is the desirability of dissolving scaly formations, and of moisturizing the dried horny layer. Urea plays an important part in this. By its keratolytic action it facilitates sloughing off of scaly formations (Ernst, T.-M., 1981, Z. Hautkrankheiten, 56, 18:1197-1206). Further, urea has hydrating capability, promoting improved water uptake by the horny layer, which substantially ameliorates symptoms, particularly in psoriasis patients.
Studies of the penetration kinetics of dithranol have shown that the substance penetrates much faster into the damaged skin of psoriasis lesions than into normal skin. This suggests a technique of treating psoriasis whereby after a short period of application of a topical dithranol preparation, the residue on the surface is removed, thereby substantially reducing the amount of dithranol which penetrates to healthy skin. The side effects such as strong skin irritation and reddening suffered by healthy skin are thus appreciably avoided. These side effects often lead to interruption of therapy. The therapeutic results of this short time therapy (which was called "minute therapy" by Runne and Kunze) were judged equal to those of classical long-term application of dithranol preparations (Runne, U. and Kunze, J., 1982. Brit. J. Dermatol., 106:135-139; and 1985, Der Hautartzt, 36:44-46).
A prerequisite for the above-described therapy ("minute therapy") is good removability of the preparation employed. There is no suitable preparation available which has an active life of typical length required for commercial distribution, and which can be readily removed. Accordingly, one resorts to a second, inert creme, which is used to apply the material; and then this is removed with detergents. In order to facilitate wide use of the "minute therapy" for treating psoriasis, particularly in hairy areas of the body, there is a need for a topical preparation which allows the time of exposure to be accurately controlled by removing said preparation by simple rinsing.